Summary of Work: The goal of this work is to identify and characterize dietary/nutrient factors and regimens that modulate the expression of environmentally induced oxidative stress in normal and diseased states. Work to date has focused specifically on one important aspect of the diet--calories. We have recently shown that calorie restriction mitigates chemical induced oxidative stress in animal models of dust-mite induced allergy. Caloric restriction has been shown to alter a broad range of immunological endpoints in both experimental animals and humans. The objective of this work was to investigate the effect of short-term moderate feed restriction (25% reduction) on allergic immune responses in Brown Norway rats. After three weeks of acclimation to their feed regimens, rats were sensitized and two weeks later challenged with house dust mite antigen (HDM) via intratracheal instillation. Feed restriction resulted in lower levels of antigen-specific IgE in serum and reduced antigen-specific lympho-proliferative activity in pulmonary lymph nodes. Feed restriction also attenuated pulmonary inflammation as evidenced by lower levels of lactate dehydrogenase and total protein, decreased infiltration of neutrophils and eosinophils, and reduced secretion of proinflammatory cytokine TNF-a in bronchoalveolar lavage (BAL) fluid. In addition, feed restriction decreased TNF-a secretion in serum, and mRNA expression of TNF-a and IL-6 in pulmonary lymph nodes. We conclude that feed restriction strongly dampened the allergic immune responses to HDM in rats and this attenuation was associated with decreased expression and secretion of pro-inflammatory cytokines. This work is significant because it suggests that there are energy-related set-points which amplify/attenuate environmental stresses. The fact that we have shown this same effect in three unrelated exposure models indicates that this is likely to be a general phenomenon.